The End of Alzheimer's
The First Programme to Prevent and Reverse the Cognitive Decline of Dementia
Dale Bredesen (2017) Penguin Random House, London.
308 pages, £16.99.  ISBN: 9781785041228

Alzheimer’s – the very word is enough to bring on a measure of fearful anxiety, especially if you are over 65.  And so it should because, according to Dale Bredesen in the opening pages of this book, it is ‘the only one of the Western world’s ten most common causes of death for which there is no effective treatment’ (p. 4).  Moreover, ‘… it’s not “only” fatal.  Alzheimer’s is worse than fatal.  For years and sometimes decades before it opens the door to the grim reaper.’  In the meantime, ‘Alzheimer’s disease robs its victims of their very humanity and terrorizes their families.  All gone, in a grim and unrelenting descent into a mental abyss where they no longer know their loved ones, their past, the world, or themselves’ (p. 5).

The Scientific Background
For the last 50 or so years, molecular biology has made huge strides in understanding the causes of, for example, various cancers and cardiovascular diseases and it has begun to develop effective treatments.  Not so with Alzheimer’s.  Sure, it has been linked to the formation of amyloid plaques in the brain and this so-called amyloid hypothesis has become scientific dogma.  Yet laboratory and clinical trials costing billions have tested thousands of potential drugs either to inhibit the development or accelerate the destruction of these plaques, but to almost no avail.

True, there are a few drug treatments using, for instance, donepezil or memantine.  Here is their underlying big idea.  Acetylcholine is a key brain chemical that operates as a neurotransmitter, signalling from one neuron to another, allowing us to think, remember, see, move, and so on.  This acetylcholine is destroyed by the enzyme cholinesterase, but donepezil is a cholinesterase inhibitor, an enzyme that can stop the destruction of acetylcholine.  If Alzheimer’s is associated with a lack of acetylcholine, then inhibiting its destruction might lessen the effects of the disease.  Donepezil sort of works, but not sufficiently effectively.  Memantine functions similarly via the neurotransmitter called glutamate.  Neither drug stops Alzheimer’s worsening, and they are certainly not cures.

The Bredesen Claims
Herein, one of the fundamental obstacles to treating Alzheimer’s.  It is not a single disease.  Though symptoms may be similar, there are at least three important subtypes and each, according to Bredesen, needs a different approach.  Yet on page 10, he declares his hand, ‘Let me say this as clearly as I can: Alzheimer’s disease can be prevented, and in many cases its associated negative decline can be reversed.’  That is the boldest of bold claims, and it is the very substance of this book, appropriately subtitled, The First Programme to Prevent and Reverse the Cognitive Decline of Dementia.

Bredesen further claims that ‘Alzheimer’s arises from an intrinsic and healthy downsizing programme for your brain’s extensive synaptic network.  But it is a programme that has run amok.  In Alzheimer’s, an otherwise normal brain-housekeeping process has gone haywire’ (p. 13).

The ReCODE Protocol
Enter ReCODE, the Reversal of COgnitive DeclinE.  This is what Bredesen calls ‘a sophisticated personalized protocol based on our decades of research on the neurobiology of Alzheimer’s disease’ (p. 13).  Much of this protocol was devised in response to the results of a simple case study with ten patients reported in a 2014 paper entitled, ‘Reversal of cognitive decline: a novel therapeutic program’, by Dale E Bredesen and published in Aging (2014) 6: 707-717.  There were also two additional follow-up papers published in 2016 and 2018 in Aging and The Journal of Alzheimer’s Disease & Parkinsonism respectively.  These are not, contrary to Bredesen’s assessment (p. 10), ‘leading medical journals’.  Indeed, none of these three papers includes a Methods section so the work cannot be repeated and verified by others, which is the very touchstone of all experimental science.  In addition, there is no record of how patients were selected.  Who were included or excluded?  What stage of Alzheimer’s did they have?  And what about non-responders?  Did everyone on the ReCODE programme really improve, and if so, to what extent?  All this is a somewhat shaky foundation for the construction of such an allegedly radical therapy.  Is this hard science?

Are these researchers hard scientists?  What are Bredesen’s and his co-workers’ academic credentials?  They were apparently conventionally educated and mostly employed by the Department of Neurology, University of California and the Buck Institute for Research on Aging, California.  The latter is a well-endowed not-for-profit organisation that undertakes research on aging and age-related diseases.  Dale Bredesen was its founding president as well as the CEO of Buck.  He now heads its laboratory which is focused on Alzheimer’s disease.  In other words, these investigators are traditionally-trained, biological scientists, not medical charlatans.

ReCODE Described
However, ReCODE turns out to consist mostly of unsophisticated sampling and testing of patients’ metabolites, giving low-tech food supplements and promoting some simple lifestyle changes.  ReCODE is branded as a ‘direct-to-consumer intervention’.  It is administered, somewhat confusingly, through Apollo Health and other affiliates, such as CogMission.  The latter, based in Edinburgh, offers Bredesen protocol basic assessments, laboratory tests and contacts with trained practitioners for £3,600, which, with average add-ons, can, according to its website, mean ‘the cost per day is £32’, or £11,680 per year, plus a monthly subscription fee of £500, all ’payable monthly by standing order.’  There are also likely to be retesting fees and the addition of a host of available options including, for example, cognitive games and online support.  The latter even offers ‘a brain-healthy, fully prepared, chef-curated cuisine by Nutrition for Longevity.  KetoFLEX 12/3 provides nutritional support for cognitive health … to optimally fuel your brain.’  These are hardly the expected components of a scheme heralded as revolutionary for the prevention and reversal of Alzheimer’s.  Surely, we were expecting some serious, novel hi-tech genetic engineering, stem-cell technologies, neural transplants, potent biotech drugs and so forth.

Still undeterred, Bredesen maintains that ‘Alzheimer’s disease is actually a protective response to, specifically, three different processes: inflammation, suboptimal levels of nutrients and toxic exposures’ (p. 16).  Subscribers to ReCODE are first subjected to a battery of tests, known as Cognoscopy, in order to define their personal causal factors.  The resulting risk profiles then provide the bases for optimizing their personal treatments to prevent and reverse their cognitive decline.  Once recruited onto ReCODE, they are offered (of course, the sceptic would say) extra possibilities ‘to achieving the very best results and to sustaining that improvement’ (p. 17).  Ka-ching!!  Some would call it ‘preying on the vulnerable’.  Nevertheless, Bredesen further pronounces (p. 18), ‘What the research from my laboratory colleagues and me adds up to is this: No one should die from Alzheimer’s disease.’

Here ended the book’s first 19 pages – 289 to go.  What had so far been a decent outline of Alzheimer’s disease and the ReCODE protocol, the book now descends into chapter after chapter of numerous diagrams, interminable lists and descriptions of various nutrients and enzymes, basic biology, potential add-ons, biographies and personal testimonies.  The latter are a mainstay of Bredesen’s work, yet these subjective assessments of cognitive function are not only susceptible to selection bias, but they are also generally regarded as unreliable.  Such apocryphal information, anecdotal narrative and hearsay evidence have no part in hard science.

It was all too much for me – I gave up and put the book down.  After a while, I did pick it up again to flip and scan the remaining pages.  Obviously, this was not a great read for me.  Yet The End of Alzheimer’s has sold amazingly well.  It has appeared on numerous best-selling book lists with thousands of 5-star ratings on, for instance, Amazon.  It seems almost impudent to question such a popular read.  But I shall.

ReCODE Questioned
At this point I became uneasy.  Is ReCODE akin to those internet healthcare scams, like those claiming to cure worn-out knees, problematic prostates, uncontrolled obesity and so forth?  Are subscribers being taken for a pecuniary ride?  Undaunted, Bredesen brashly asserts, ‘Here, finally, is nothing less than the first good news about Alzheimer’s disease’ (p. 16).  Here, surely is hype and hyperbole.  After all, if ReCODE really does prevent and reverse Alzheimer’s, why has not mainstream medicine adopted it or, at least, subjected it to the rigours of extensive clinical trials?  I am sorry to say that there are millions of people around the world suffering from diverse, incurable diseases.  They have tried conventional, evidence-based therapies but, for various reasons, relief has remained elusive.  They are the cohort who are particularly susceptible to being persuaded to try alternative remedies.  Their ‘proof’ is typically based on pseudoscience and subjective evidence.  What level of verification is needed by such sufferers of Alzheimer’s?

There are numerous additional questions surrounding Bredesen and his ReCODE protocol.  First, and above all, as already mentioned, why has ReCODE not been adopted mainstream?  Second, how have the claimed brain improvements been measured?  Third, could they have been caused by the placebo effect, which can be notoriously driven by patient expectation.  Fourth, where are the expected positive and negative peer-reviewed research papers?  Fifth, where are the independently-published studies that test Bredesen’s hypotheses?  Sixth, if ReCODE is truly revolutionary, why have supporting research papers not appeared in the world’s top-rated scientific and medical journals, like Nature and The Lancet?  Seventh, why does ReCODE look like a business proposition?  Eighth, what other human disease therapy relies on a business model for treatment?

In Conclusion
There are elements of the ReCODE protocol that can be both beneficial and health promoting.  For instance, it is well-known that exercise, good nutrition, social engagement, and so on, can help keep the brain attuned.  In addition, these strategies are largely cost-free for patients.  However, seriously-ill people can commonly hold some unorthodox and irrational beliefs.  They understandably seek positive interventions for what are mostly currently incurable diseases.  And, having tried and abandoned much of conventional medicine, such beliefs can be forcefully compelling in a realm with little or no hope.

So far in the twenty-first century, doctors still cannot cure Alzheimer’s disease, but they can provide patients with some, albeit minor, positive treatments and palliative care to moderate cognitive decline.  On the other hand, patients should be warned by doctors against adopting unrealistic expectations and reliance on unproven therapies.

So how does the ReCODE, the Bredesen protocol, measure up?  Undoubtedly, some, on the basis of its huge fanbase of loyal supporters, subscribers and consumers, would evaluate it as successful.  Others would call it a mixture of common sense and unproven methodology.  And a number would judge it to be a scientifically unsound, ethically dubious and financially costly intervention.  As such, it is a plan from which it is best to stay away.  At least, that’s what I plan to do!

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